Symptoms of anxiety and depression in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

Genomic imbalances defining novel intellectual disability associated loci.

BACKGROUND: High resolution genome-wide copy number analysis, routinely used in clinical diagnosis for several years, retrieves new and extremely rare copy number variations (CNVs) that provide novel candidate genes contributing to disease etiology. The aim of this work was to identify novel genetic causes of neurodevelopmental disease, inferred from CNVs detected by array comparative hybridization (aCGH), in a cohort of 325 Portuguese patients with intellectual disability (ID). RESULTS: We have detected CNVs in 30.1% of the patients, of which 5.2% corresponded to novel likely pathogenic CNVs. For these 11 rare CNVs (which encompass novel ID candidate genes), we identified those most likely to be relevant, and established genotype-phenotype correlations based on detailed clinical assessment. In the case of duplications, we performed expression analysis to assess the impact of the rearrangement. Interestingly, these novel candidate genes belong to known ID-related pathways. Within the 8% of patients with CNVs in known pathogenic loci, the majority had a clinical presentation fitting the phenotype(s) described in the literature, with a few interesting exceptions that are discussed. CONCLUSIONS: Identification of such rare CNVs (some of which reported for the first time in ID patients/families) contributes to our understanding of the etiology of ID and for the ever-improving diagnosis of this group of patients.

Discondrosteose de Léri-Weill: importância do exame físico / Léri-Weill dyschondrosteosis: importance of physical examination

OBJETIVOS: Descrever um caso de Discondrosteose de Léri-Weill, uma displasia óssea hereditária rara, frequentemente associada a uma haploinsuficiência do gene SHOX (short stature homeobox-containing). DESCRIÇÃO DO CASO: Criança de três anos, sexo feminino, enviada à consulta de pediatria por suspeita de hipertensão arterial. Antecedentes pessoais e familiares irrelevantes. Ao exame físico apresentava aspeto dismórfico, com encurtamento dos membros superiores e inferiores, mãos e pés pequenos e pescoço curto. A hipertensão arterial não foi confirmada. O estudo genético para excluir cromossomopatia revelou mutações no gene SHOX compatíveis com Discondrosteose de Léri-Wei. CONCLUSÕES: O exame físico é fundamental na prática clínica, permitindo identificar alterações importantes que nem sempre são o motivo da consulta. Na Discondrosteose de Léri-Weill o pronto diagnóstico e a orientação adequada são fundamentais, sobretudo pelas implicações terapêuticas desse distúrbio, que apresenta evolução favorável se tratado com hormônio do crescimento.

AIMS: To report a case of Léri-Weill dyschondrosteosis, a rare hereditary bone dysplasia often associated with a haploinsufficiency of the SHOX (short stature homeobox-containing) gene. CASE DESCRIPTION: A three-year-old female had sought medical care for hypertension. Irrelevant personal and family background. The physical examination showed dysmorphic aspect with shortening of arms and legs, small hands and feet, and short neck. Hypertension was not confirmed. Genetic study for chromosomal deletion syndromes revealed mutations in the SHOX gene compatible with Léri-Weill dyschondrosteosis. CONCLUSIONS: Physical examination is essential in clinical practice, allowing the identification of majorchanges that are not always the reason for the medical appointment. Early diagnosis and proper guidance are essential in Léri-Weill dyschondrosteosis, especially because of its therapeutic implications. The outcome is favorable if the disorder is treated with growth hormone therapy.

Validation of control of allergic rhinitis and asthma test for children (CARATKids)--a prospective multicenter study.

BACKGROUND: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. METHODS: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires' results. Data-driven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. RESULTS: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was -1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and -0.69 and met the a priori predictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46. CONCLUSION: CARATKids showed adequate psychometric properties and is ready to be used in clinical practice.